This study led by the Calkhoven lab describes that the transcription factor C/EBPα is a key mediator of SIRT1-controlled transcription of mitochondrial genes, which results in increased mitochondrial respiration. SIRT1 is activated in times of energy demand by high levels of NAD+ and its activation is associated with increased health and lifespan. This work further reinforces the important role C/EBP transcription factors play in controlling energy homeostasis and related lifespan regulation.